Summary Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. At least 40%, and up to 70%, of cancer patients treated with standard chemotherapy regimens or upper-body radiation develop oral mucositis. Intensity modulated RT (IMRT) lessens chronic side effects, but not the acute toxicity seen in oral mucosa. The new Stereotactic Body RT (SBRT) that directs RT to the tumor mass should reduce oral mucositis, but this will not apply to patients who need chemotherapies, targeted therapies, or conventional RT. The immunotherapy is gaining momentum for cancer therapy, but oral mucositis appears to occur more often with immunotherapy. To date, Palifermin, a protein derived from keratinocyte growth factor, is the only targeted therapy approved by the Food and Drug Administration (FDA) for preventing oral mucositis in patients with hematopoietic malignancy followed by bone marrow transplant (4% of the at-risk population), but it has no effect on existing mucositis. Allander Biotechnologies has developed a proprietary biologic that shows prophylactic and therapeutic effects on radiation-induced oral mucositis in mice upon topical application to oral mucosa. Our biologic possesses multiple functions needed for oral mucositis healing. In the Phase I funding period of this grant, we have developed the biologic production system and demonstrated that treating mice with this biologic alleviated radiotherapy-induced oral mucositis but did not compromise its killing of adjacent oral cancer. In this Phase II application, we will establish the scale-up process and quality controls for manufacturing our biologic. We will generate efficacy data to optimize pharmacodynamics (PD) biomarkers. We will generate preliminary toxicity data to design pharmacokinetics (PK) and toxicology studies required for filing an Investigational New Drug (IND) application. By the end of Phase II funding, we will have established manufacturing procedures for our biologic and protocols (analytical, bioassay, PK and toxicology) ready for generating additional IND data under Good Laboratory Practice (GLP) conditions.